B2 SINE retrotransposon causes polymorphic expression of mouse 5-aminolevulinic acid synthase 1 gene.
5-Aminolevulinic acid synthase 1 (ALAS1) is the key enzyme in the homeostasis of nonerythroid heme and of fundamental importance in respiration, the metabolism of drugs, chemicals and steroids and cell signalling. The regulation of ALAS1 in response to stimuli occurs at transcriptional, translational and post-translational levels which could depend on inter-individual variation in basal expression. A genetic difference in hepatic ALAS1 mRNA levels between C57BL/6J and DBA/2 mice was detected by microarray and was >5-fold in whole liver or hepatocytes when estimated by qRT-PCR. Analysis of the ALAS1 promoter showed a 210 nt insert in the DBA/2 containing a B2 SINE retrotransposon causing a marked repression of expression by intracellular reporter systems. Deletions across the B2 SINE demonstrated that the full sequence was required for transcriptional inhibition. The findings show that a B2 SINE can contribute to the regulation of ALAS1 and SINEs in 5'-UTR regions contribute to inter-individual differences in gene expression.
Chernova
Tatyana
T
MRC Toxicology Unit, University of Leicester, Leicester, UK.
Higginson
Fiona M
FM
MRC Toxicology Unit, University of Leicester, Leicester, UK.
Davies
Reginald
R
MRC Toxicology Unit, University of Leicester, Leicester, UK.
Smith
Andrew G
AG
MRC Toxicology Unit, University of Leicester, Leicester, UK. Electronic address: ags5@le.ac.uk.
D020121:5' Untranslated Regions / Q000235:genetics*; D000624:5-Aminolevulinate Synthetase / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018626:Retroelements / Q000235:genetics / Q000502:physiology*
D020121:5' Untranslated Regions; D018626:Retroelements; D000624:5-Aminolevulinate Synthetase